Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies

Abstract

Objectives: Lipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs.

Methods: Lipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study. The effect of statin therapy on lipid levels was evaluated in patients on statins at baseline and in patients who initiated statins during the study.

Results: Treatment with baricitinib was associated with increased levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL and decreased small, dense LDL particle numbers and GlycA. Lipid changes from baseline were not significantly different between baseline statin users and non-users. In patients who initiated statin therapy during the study, LDL-C, triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre-baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated.

Conclusions: Baricitinib was associated with increased LDL-C, HDL-C and triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of cardiovascular event rates during long-term treatment is warranted to further characterise these findings and their possible clinical implications.

Trial registration number: NCT00902486, NCT01469013, NCT01185353, NCT01721044, NCT01721057, NCT01711359, NCT01710358, NCT01885078.

Keywords: DMARDs (biologics); lipids; rheumatoid arthritis.

Conflict of interest statement

Competing interests: PCT reports personal fees from Eli Lilly and Company during the conduct of the study; grant support from Celgene and Galapagos, grant support and personal fees from UCB Pharma, and personal fees from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer and Takeda outside the submitted work. JMK reports grant support and personal fees from Eli Lilly and Company during the conduct of the study; grant support from Pfizer and Novartis, grant support and personal fees from Eli Lilly and Company; and other support from Corrona outside the submitted work. PE reports grant support and personal fees from Eli Lilly and Company during the conduct of this study and grant support from Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung and Sandoz. SHZ, GR, LC, SW, CS, MK, WLM, DES, TPR and SdB are full-time employees and stockholders of Eli Lilly and Company. JZ is employed by IQVIA with which Eli Lilly and Company contracts for clinical trial and statistical support. JDO reports employment by LabCorp during the conduct of the study. In addition, JDO is an inventor on an issued patent: NMR measurements of GlycA. MAC is an employee of LabCorp. IBM reports grant support and personal fees from Eli Lilly and Company during the conduct of this study and grant support from AbbVie, Pfizer, Novartis, Roche, Janssen and Pfizer.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Lipid profile for total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein A-I and apolipoprotein B in patients from the six-study placebo-controlled set. Data in line graphs are absolute values at baseline, week 12 and week 24 with data censored at rescue; mean (SD) for all lipids except triglycerides, which are median (25th, 75th percentiles). Patients on placebo who were rescued to baricitinib before week 24 were not included in this analysis. Inset bar charts show mean per cent change from baseline to weeks 12 and 24 with data censored at rescue. *P≤0.05, ***P≤0.001 versus placebo. HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Figure 2

Lipid profile in patients who initiated statins during the phase III studies of the six-study placebo-controlled set including data in the long-term RA-BEYOND study for the baricitinib doses. Data are absolute values at three milestones: baseline, initiation of statin therapy and end of statin treatment or study period; mean (SD) for all lipids except triglycerides, which are median (25th, 75th percentiles). HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.